OBJECTIVE: To compare the expression of cytokeratins (CKs) 6, 16, 19 and pan-cytokeratin (PAN) in oral mucosa cells between smokers and nonsmokers to determine the proliferative activity and expression indicative of a potential for malignant transformation.STUDY DESIGN: Smears were obtained from the kit lateral border of the tongue with a cytobrush from 25 smokers and 20 nonsmokers seen at the clinics of Silo Jose dos Campos Dental School, São Paulo State University, Sao Jose dos Campos, Silo Paulo, Brazil, and processed for immunohistochemistry. Conventional microscopy was used for qualitative analysis. Proportions were compared statistically by the z-test and Fisher's exact test.RESULTS: The expression of CK6 (p = 0.002), CK16 (p = 0.003), CK19 ( p = 0.0001) and PAN (p = 0.008) was higher in oral mucosa smears from smokers compared to nonsmokers.CONCLUSION: The expression of CK6 and CK16 demonstrated increased epithelial proliferation in the oral mucosa of smokers, and expression of CK19 indicated alterations in epithelial maturation. The expression of PAN indicates the need for the investigation of other types of CK in further studies. (Anal Quant Cytol Histol 2011;33:19-24)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP